The genetics of venous thromboembolism: a systematic review of thrombophilia families

Zhang, Yu; Zhang, Zhu; Shu, Shi; Niu, Wenquan; Xie, Wanmu; Wan, Jun; Zhai, Zhenguo; Wang, Chen

doi:10.1007/s11239-020-02203-7

Cited by 9 publications

(6 citation statements)

References 79 publications

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“…Other loci such as non-O blood (ABO), fibrinogen gamma (FGC) and hyperhomocystenemia (MTHFR) have since been associated with increased VTE risk. Many more loci associated with increased VTE risk continue to be discovered through genome-wide association [31][32][33][34][35] .…”

Section: -Are There Genetic Predisposing Factors For Vte?mentioning

confidence: 99%

“…Factor V Leiden is due to resistance to activated protein C (APC-resistance) on Factor V. When inactivated protein C attaches to thrombin, APC is formed and inactivates Factor Va and VIIIa by cleaving specific sites. The most common mutation, rs6025, is due to a single-point mutation that replaces arginine with glutamine at the APC cleavage site 31,41 . Factor V Leiden mutation is the most common thrombophilia and has been estimated to be associated with up to 20% of patients with first VTE events 37 .…”

Section: - Are There Genetic Predisposing Factors For Vte?mentioning

confidence: 99%

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Recommendations from the ICM-VTE: General

2022

Journal of Bone and Joint Surgery

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Section: -Are There Genetic Predisposing Factors For Vte?mentioning

confidence: 99%

Section: - Are There Genetic Predisposing Factors For Vte?mentioning

confidence: 99%

Recommendations from the ICM-VTE: General

2022

Journal of Bone and Joint Surgery

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“… [9] Various genetic defects have been identified to account for hereditary thrombophilia, including factor V Leiden, prothrombin G20210A mutation, protein C deficiency, and protein S deficiency. [10] The prevalence of pathogenic genes varies among different ethnic groups. Factor V Leiden and G20210A mutations are almost exclusively identified in Caucasian populations, while deficiency of natural anticoagulants occurs more frequently in Asian populations.…”

Section: Discussionmentioning

confidence: 99%

“…Hereditary thrombophilia constitutes a major risk factor for unprovoked VTE and its recurrence [9] . Various genetic defects have been identified to account for hereditary thrombophilia, including factor V Leiden, prothrombin G20210A mutation, protein C deficiency, and protein S deficiency [10] . The prevalence of pathogenic genes varies among different ethnic groups.…”

Section: Discussionmentioning

confidence: 99%

Rapid identification of a pathogenic variant of PROS1 in a thrombophilic family by whole exome sequencing

2021

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Rationale: Venous thrombosis remains a significant problem in modern days. Genetic factors contribute to a subset of patients with venous thrombosis. It is sometimes challenging to identify the underlying culprit in thrombophilic individuals based on traditional laboratory testing and Sanger sequencing. Patient concerns: A thrombophilic family presented with multiple venous thrombosis was examined. Diagnoses: Molecular genetic analysis revealed a pathogenic missense variant of the PROS1 gene. Based on this finding and clinical manifestations, a final diagnosis of protein S deficiency was made. Interventions: Whole exome sequencing (WES) of the proband was performed to identify disease-causing variants. Subsequently, Sanger sequencing was performed to validate the variant in the affected members. Outcomes: Using WES, we rapidly identified a proven pathogenic missense variant (c.1543C > T, p.Arg515Cys) in the sex hormone-binding globulin domain of PROS1, which was confirmed by Sanger sequencing. The decreased level and activity of protein S caused by the variant explained the phenotypes of the family. Patients received rivaroxaban as a long-term anticoagulation therapy and achieved a good prognosis. Lessons: Our study suggests WES as a rapid search strategy to identify the genetic factors underlying thrombophilic disorders. Patients with venous thrombosis caused by PROS1 mutations could receive rivaroxaban as the first choice of anticoagulation therapy.

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“… 3 In addition, genetic factors are also important in VTE development, with family-based studies showing that heritable factors account for a significant proportion of familial cases of VTE. 4 Several genetic loci have been identified by large GWAS studies to be associated with susceptibility to VTE, 5 which were included in metabolic pathways.…”

Section: Introductionmentioning

confidence: 99%